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Particular brain connections linked to positive human traits

Nov 12, 2015

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A new study by the Oxford University researchers reveals that there is a strong link between a particular set of connections in the brain and positive lifestyle and behavior traits. The findings of the study were published recently in Nature Neuroscience.

The team of researchers was led by the University’s Centre for Functional MRI of the Brain. As a part of their research, they investigated the connections in the brains for 461 people and compared them with 280 different behavioural and demographic measures that were recorded for the same participants. Their study revealed that variation in brain connectivity and an individual’s traits had a strong link; the connections in brain of people with positive lifestyles and behaviours were categorically different from the negative ones.

The data used by the team of researchers was taken from the Human Connectome Project (HCP) � it is a $30m worth NIH funded brain imaging study carried out by Washington, Minnesota and Oxford Universities. Functional MRI scans of 1,200 healthy participants along with detailed data from tests and questionnaires are being paired up in this project. Professor Stephen Smith, lead author of the paper opined that the quality of the imaging data is the biggest strength; it is unprecedented. The spatial and temporal resolution of the fMRI data is far better than previous large datasets. It has helped to keep the number of subjects for study pretty large. Till now, the data for 500 subjects have been forwarded to researchers for analysis.

The team created an average map of the brain’s processes across the participants by taking data from the 461 scans. They then studied how much all of those regions communicated and interacted with each other, in every participant. It resulted in a connectome for every subject � it showed how much the 200 separate brain regions communicate with each other. To further the study, the researchers added 280 different behavioural and demographic measures for each subject and carried out a ‘canonical correlation analysis’ between the two data sets – a mathematical process that can unearth relationships between the two large sets of complex variables.

It was found by the researchers that there is a strong correlation between specific variations in a subject’s connectome and their behavioural and demographic measures. It was seen that those with a connectome at one end of scale score highly on measures that are typically positive and those at the other end of the scale were seen to show negative traits. Examples of positive traits are vocabulary, memory, life satisfaction, income, years of education and examples of negative traits include anger, rule-breaking, substance use, poor sleep quality, etc.

The results of the study bear resemblance to ‘general intelligence g-factor’ – a variable first proposed in 1904 which was sometimes used to summarise a person’s abilities at different cognitive tasks. There are some obvious differences too – the new results include many real-life measures which were not included in the g-factor. The believers in g-factors are of the opinion that many intelligence-related measures are inter-related. But, g-factor also have received some criticism, as there is not enough clarity if these correlations between different cognitive abilities are truly reflecting correlations between distinct underlying brain circuits. The new results can shed some light on the same.

Professor Smith said that it is possible that with hundreds of different brain circuits, the tests that are used to measure cognitive ability actually make use of different sets of overlapping circuits. Researchers are hopeful that by looking at brain imaging data they will be able to relate connections in the brain to the specific measures, and work out what these kinds of test actually require the brain to do.

References

https://medicalxpress.com/news/2015-09-brain-linked-positive-human-traits.html

https://www.ox.ac.uk/news/2015-09-28-particular-brain-connections-linked-positive-human-traits

New Study Suggests Hallucinations, Alone, Do Not Predict Onset of Schizophrenia

Nov 11, 2015

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Even after years of study and research, the diagnosis of schizophrenia in its early stages has remained a mystery � from the appearance of its early symptoms to the development of the disorder in full form, it is quite difficult to point out when it spread its tentacles. A new research led by researchers at the UNC School of Medicine and the Renaissance Computing Institute (RENCI), the results of which were published online recently in the journal Schizophrenia Research has revealed that illogical thoughts as most predictive of schizophrenia risk. Surprisingly, it is also revealed that perceptual disturbances said to be the forerunners of hallucinations are not predictive, even though schizophrenia is characterized by full-blown hallucinations.

Diana Perkins, MD, a clinician and professor of psychiatry at the UNC School of Medicine and one of the first authors of the study said that the sooner people are identified of suffering from schizophrenia and the quicker they receive treatment, the better their prognosis. If people at high risk of psychosis can be identified, interventions can be developed to prevent the development of schizophrenia and the functional declines associated with it.

More than 3 million people in the United States suffer from schizophrenia. Late adolescence and early adulthood is the time when it begins and remains a chronic and disabling disorder for most patients. Psychosis refers to a group of symptoms, including paranoia, delusions (false beliefs), hallucinations, and disorganization of thought and behavior; more than 6 million people are said to experience it. Psychosis is a characteristic of schizophrenia even though it also occurs in people suffering from bipolar disorder or other medical conditions.

Mild psychosis-like symptoms are early warning signs of schizophrenia. About 15-20 percent of people who suffer from mild psychosis-like symptoms eventually develop schizophrenia or other disorders with full-blown psychosis. The current criteria for diagnosing attenuated psychosis is having one of these symptoms- illogical thoughts, disorganized thoughts, or frequent perceptual disturbances and severity to impact function.

For their study, Perkins and Jeffries examined what symptoms could predict psychosis over a two-year follow-up period in a group of 296 individuals diagnosed to be at high-risk for psychosis. Their study revealed that suspiciousness and unusual thoughts were the most predictive, and that difficulty with concentration further enhanced psychosis risk prediction.

Clark D. Jeffries, PhD, a scientist at RENCI and first author of the study said that identification of the most informative symptoms was performed with “stringent randomization tests.� The investigators also validated these findings in a new cohort of 592 people with attenuated psychosis symptoms, confirming the findings. Unusual thought content and suspiciousness include a “feeling of being watched,” fixating on coincidences that aren’t actually connected, or finding “signs” in certain experiences or having a distorted sense of time. Difficulty concentration or focus refers to problems with distractibility and short-term memory. Reduced ideational richness typically refers to difficulty following conversations or engaging in abstract thinking.

It is surprising to note that perceptual disturbances � for example: seeing shadows or hearing knocking noises with a sense that these experiences are “not real,” – were not predictive of psychosis. Such symptoms were common in those who suffer from psychosis, but they were not characteristic of the condition, which means that such symptoms were also equally common in those who did not develop psychosis.

Perkins opined that when assessing psychosis risk, this study reveals that a person's thought process must be emphasized rather than pinning on perceptual disturbances as a specific early warning sign as it may not be predictive of psychosis.

References

https://medicalxpress.com/news/2015-10-hallucinations-onset-schizophrenia.html

https://news.unchealthcare.org/news/2015/october/new-study-suggests-hallucinations-alone-do-not-predict-onset-of-schizophrenia

Molecular kiss of death flags pathogens

Nov 10, 2015

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Bacteria, viruses, fungi and other such bugs and parasites that make us sick hide in our body cells in certain protective bubble shells called vacuoles. For the body to fight and clear an infection, it should have the ability to recognize and destroy these vacuoles without affecting the rest of the living cell.

In a new study, the results of which appeared recently in the Proceedings of the National Academy of Sciences, researchers have discovered that our bodies mark pathogen-containing vacuoles for destruction by using a molecule called ubiquitin, also commonly referred to as the “kiss of death.” The findings are promising as it can lead to the creation of new therapeutic strategies to boost the immune system’s response to the pathogens that lead to human ailments, like tuberculosis, salmonella, chlamydia, toxoplasmosis and malaria.

Jörn Coers, Ph.D., senior author of the study and assistant professor of molecular genetics and microbiology at Duke University School of Medicine opined that for the body to find and get rid of these pathogens, it is like finding a needle in a haystack. The immune system must target a single microbe, in a vacuole, in an ocean of other membranes that are floating around inside the cell. The immune system does this humongous task by painting the vacuole with a coat of ubiquitin, which lets it attack the vacuole and eliminate the pathogen inside.

It is interesting to know how the whole thing happens � a pathogen when it enters a host cell cloaks itself with a part of the plasma membrane to hide its true identity. If our immune system is healthy, it will eventually discover the invasion and will place special molecules called guanylate binding proteins (GBPs) on high alert. These proteins are special because they just bind to the membranes of the pathogen-containing vacuoles and eliminate the invaders. Coers and his fellow researchers were curious to find out how the GBPs know exactly which membrane-bound structures to seek out.

A large-scale screen for proteins involved in the clearance of pathogens was carried out by the researchers. Surprisingly, they found a few proteins that play a role in ubiquitination, the process by which ubiquitin tags are put on the body’s own doomed proteins so that they can be destructed. No other previous studies had correlated ubiquitin and the destruction and elimination of pathogen-containing vacuoles by GBPs.

To further their study, Coers and his fellow researchers went ahead and looked for these ubiquitin tags on vacuoles containing two different microorganisms – Toxoplasma gondii, the single-celled parasite that causes toxoplasmosis and Chlamydia trachomatis, the causative agent of the most common sexually transmitted bacterial infection. The first thing they did was to prime the cells with cytokines � they are signaling molecules that kick the immune system into action. �The cells were then stained with a red dye that was specific for the ubiquitin protein.

Coers said that suddenly they could see the beautiful rings of ubiquitin nicely decorating the outsides of the pathogen-containing vacuoles. They then went on to identify the molecular players responsible for attaching the ubiquitin tags and for escorting the GBPs to the surface of the vacuole so they can coordinate an attack. The researchers also found that highly virulent strains of Chlamydia and Toxoplasma contain special factors which block the addition of these ubiquitin tags. Since their vacuoles don’t get ubiquitinated, the GBPs don't treat them as invaders.

Further research is needed to determine what tricks pathogens resort to, to evade the immune response. Once it is ascertained what makes some of these pathogens more dangerous, therapeutics can be designed to render these hypervirulent strains more susceptible to the host response.

References

https://medicalxpress.com/news/2015-09-molecular-death-flags-pathogens.html

https://today.duke.edu/2015/09/kissofdeath

Compound Doubles Up On Cancer Detection

Nov 9, 2015

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A study published recently in the Proceedings of the National Academy of Sciences (PNAS) has revealed that by tagging a pair of markers that is exclusive to a common type of brain cancer yields a signal which is more specific and more obvious to cancer. The results of the research from the University of Wisconsin-Madison is significant as it holds promise for a new avenue for early tumor detection which in principle is likely to be applicable to a variety of cancers. Another feather in their cap is that the cancer treatment methods it suggests are more precise.

Haiming Luo, a UW-Madison postdoctoral researcher in the Department of Radiology and first co-author of the study�shared that the idea of searching for two markers of cancer has been there for a while, but technically it was quite difficult to achieve the same.

The researchers under the direction of Weibo Cai, an associate professor of radiology and medical physics in the UW School of Medicine and Public Health and biomedical engineering in the UW College of Engineering were successful in creating antibodies which are specific to two proteins that often characteristic of brain tumors. One of these markers is called CD105 and it appears on new blood vessels that grows only in pregnancy in adult humans or at times when wounds heal. The other marker – epidermal growth factor receptor when mutated spark uncontrolled cell division in a wide range of cancers including glioblastoma.

In order to induce the ability to bind to both these markers in a structure, the researchers severed unneeded sections of each antibody, and later assembled them with a fast, reliable joint. The structure also had a fast-decaying isotope that is detectable in a PET (positron emission tomography) scanner.

Once the detection compound was purified to do away with unpaired antibodies, the remains of it were injected into mice with epidermal growth factor receptor. The researchers then waited for about 36 hours to let the detector molecules to link to tumours or to clear from normal tissue. PET scanner was then used to find the radiation they released. It was found that there was a great increase in the intensity of the signal as compared to conventional PET scanning. The other benefit was specificity � while the detector linked to tumors, but they didn't connect to healthy tissue.

Typically, when PET scans are used for detecting cancer, the signal they look for is glucose metabolism- it is a biological activity that characterizes cancer or its possible causes. However, in brain various activities can mask the signal of cancer which makes cancer detection quite difficult.

Reinier Hernandez, a graduate student in medical physics and first co-author of the study opined that the study points toward a “toolkit” approach to cancer detection. He also said that studies on other tumors are moving forward based on well-known targets on particular cancers that appear in genetic databases.

Hernandez said that the new technique demonstrates a novel way to connect to tumor cells while avoiding normal tissue, and thereby it suggests a way to treat cancer rather than just identifying it. Specific treatment should eventually replace chemotherapy which doesn't just damage tumors but healthy tissues as well.

Cai opined that as an example, the two-part antibody could be joined to a strong, quick-acting unit of radiation, or to a chemical that can kill cells. They can make use of detector to assess the progress of treatment. He also added that with so much research happening in the field, we learn more about cancer and how it is different from healthy tissue. Thus, we are better equipped to detect and manipulate genes, proteins and other molecules, both for detection and for therapy.

References

https://medicalxpress.com/news/2015-10-compound-cancer.html

https://news.wisc.edu/24076

Vaccination on the Horizon for Severe Viral Infection of the Brain

Nov 8, 2015

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The human body is home to a multitude of viruses and bacteria. Some of them house themselves in the gut, others on the skin and other body organs. They are often needed in important bodily functions, but, under certain circumstances some can also cause diseases. One such example is the JC virus, a member of the polyoma tumor virus family, which causes a rare and fatal disease called progressive multifocal leukoencephalopathy (PML).

In a new research, scientists from the University of Zurich and the University Hospital Zurich have revealed that they have found what they believe could be possible new treatment methods for this rare brain disease. They have discovered the specific antibodies that play a key role in combating the viral infection. The good news is that a vaccine against the disease “progressive multifocal leukoencephalopathy” could now be developed.

It is estimated that more than 60 percent of the global population are infected with this virus and it typically lives in the kidneys and some other organs. This virus can cause the PML infection in the brain, which, in most circumstances, is fatal. The main cause behind this infection is a weak immune system.

An international team of researchers which includes researchers from the University of Zurich, the University Hospital Zurich, the National Institutes of Health in the USA, San Raffaele Hospital in Milan, the University of Tübingen, and the UZH spin-off Neurimmune conducted two studies and found that the antibodies in PML patients often fail to recognize the JC virus they are infected with. Roland Martin, professor of neurology at the University of Zurich explains that in normal healthy people, the immune system keeps it in check and does not let it spread its tentacles. However, in people suffering from conditions like tumors, leukemia, AIDS, autoimmune diseases, the immune system is compromised and the JC virus gets the opportunity to alter its genetic information and infect the brain.

It is seen that in multiple sclerosis (MS) patients, when they are treated with a particular antibody, TysabriTM, it prevents immune cells from reaching the brain � and at the same time, it also inhibits the brain’s immunosurveillance. Sensing the opportunity, the JC virus enters the brain during the treatment undetected, and causes PML. This is in fact the most significant side effect of the otherwise highly effective TysabriTM. Since, there is no effective treatment for PML infection; many MS patients who develop PML infection meet a fatal end. The only means by which the JC virus can be removed from the brain is by restoring the immune system function completely.

Through their study, the researchers have now found potential ways to vaccinate against PML preventatively. In case, the brain is already infected, they have developed a means to treat it with virus-specific human antibodies. Martin explained that they managed to isolate antibody-producing cells from a patient who survived PML and used them to produce neutralizing antibodies against the JC virus. The advantage these human antibodies have is that they recognize the most important mutants of the JC virus that can cause PML.

They vaccinated mice and a PML patient with the virus’ coating protein, and were able to demonstrate that the antibody response was so strong that the patient was soon able to eliminate the JC virus. This breakthrough active vaccination method has been developed at the University of Zurich and the University Hospital Zurich, and has already been used successfully on two more patients. The JC-virus-specific antibodies for the treatment of the existing brain infection were developed by the group at the University of Zurich and the University Hospital Zurich together with colleagues from the University of Tübingen and the biotechnology company Neurimmune in Schlieren.

References

https://medicalxpress.com/news/2015-09-vaccination-horizon-severe-viral-infection.html

https://www.mediadesk.uzh.ch/articles/2015/auf-dem-weg-zu-einer-impfung-bei-schwerer-virusinfektion-des-gehirns_en.html

Researcher Explores the Science of Aging

Nov 7, 2015

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A fist-sized clam found off the coast of Maine is known to live 500 years or longer, while the longest-lived human have not lived much more than 120 years. So, what does the ocean quahog knows about healthy aging which is not known to humans? Such questions drives Steven Austad, Ph.D., chair of the Department of Biology in the UAB College of Arts and Sciences and associate director of the UAB Comprehensive Center for Healthy Aging, to research in the area to unravel the mystery of healthy aging.

The aim of Austad’s studies in comparative gerontology, which look to long-lived animals, is to identify new molecular targets to help humans. His research focuses on understanding the underlying causes of aging at the molecular level.

A part of his research includes the work on a book called Methuselah’s Zoo, which Austad describes as “a natural history of successful aging.” This book is going to have the profiles of long living creatures like 500-year-old clams, 200-year-old whales and 40-year-old bats.

More than a dozen species of clams have lifespan of 100 years of more. They are technically bivalve mollusks and are known to live longer than any other animal groups. However, not all clams live to such an age. For this study, Austad’s lab is studying mitochondrial function, protein stability and stress resistance across seven species of clams, the lifespans of which ranges from a year to the ocean quahog’s 500-plus years.

Austad work led him to find one of the key causes of slow aging, which is to protect the protein inside our cells. Proteins have to be folded precisely to make everything inside the cell work well. But, as we age, they get battered and eventually lose their precise shape. Austad found that ocean quahogs keep their proteins in shape century after century. To experiment further, Austad took human proteins and added them to a mix of tissues from the clams and found that they became more stable and hence, less likely to unfold.

Austad lab is now working to find out exactly what protects the clams’ proteins, which they feel could point to a potential treatment for aging. It could also open avenues for new therapies for conditions caused by protein misfolding like Alzheimer’s disease, etc.

Austad is also studying a tiny freshwater creature called a hydra, which does not age typically. But, recently it was found that one particular species of hydra that begins to age rapidly under the certain combination of environmental conditions. His lab is now working to discover the molecular mechanisms that get switched on, or off, as the hydra’s environment changes. Austad is hopeful that such study will help them to identify new genes that might be targets for new drugs to keep people healthy longer.

Austad, scientific director for the American Federation for Aging Research opined that today we know a lot of things from animal work that will slow aging by 20 percent. That is incredible as there is a huge difference between being healthy for 60 years and being healthy for over 70 years.� By treating the underlying causes of aging, we can push back cancer, heart disease, blindness, hearing loss and other such diseases associated with aging and make life healthier.

Another interesting lead, being followed by Austad is the drug rapamycin; a number of studies, from yeast, worms and mice, have shown that rapamycin can extend lifespan as well. Rapamycin is a FDA-approved drug to prevent rejection after organ transplants. In mice, it prevents cancer, heart disease, Alzheimer’s�a whole host of things. Even though these findings are exciting, there is a need to exercise caution too. For example, rapamycin has several side effects in mouse studies, like an elevated incidence of cataracts, loss of glucose sensitivity and testicular atrophy. More studies and research is needed to find out the right dosing and formulation that can overcome these issues in humans.

References

https://medicalxpress.com/news/2015-09-explores-science-aging.html

https://uab.edu/news/focus-on-patient-care/item/6521-answers-to-age-old-questions-austad-explores-the-science-of-aging

New Study Provides Key Insights into Aspirin’s Disease-Fighting Abilities

Nov 6, 2015

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Aspirin

The beneficial health effects of Aspirin � one of the oldest and the most commonly used medicines, have been quite a mystery to physicians. A recent study has now found that the main ingredient in aspirin targets the activities of an inflammatory protein associated with a wide variety of diseases. It has been discovered that aspirin’s main breakdown product, salicylic acid, blocks the protein, HMGB1, which could be the reason behind the drug’s therapeutic properties. It is hoped that this discovery could be instrumental in developing more powerful aspirin-like drugs. The results of the study were published in the journal Molecular Medicine.

The research was carried out by scientists at the Cornell University-affiliated Boyce Thompson Institute (BTI) in collaboration with colleagues at Rutgers and Italy’s San Raffaele University and Research Institute.

Daniel Klessig, a professor at BTI and Cornell University and study's senior author said that we have found out a key target of aspirin’s active form in the body – salicylic acid blocks the protein, HMGB1, which is associated with many prevalent diseases, like rheumatoid arthritis, heart disease, sepsis and cancers, like colorectal cancer and mesothelioma.

It has been known since long that aspirin blocks the enzymes cyclooxygenase 1 and 2, which produce hormone-like compounds that cause inflammation and pain, thereby giving a pain relieving effect. But, the body rapidly converts aspirin to salicylic acid, which is in effect, a less potent inhibitor of cyclooxygenase 1 and 2 than aspirin. Still, the effects of salicylic acid are same as aspirin, which suggests that salicylic acid may interact with additional proteins.

For the current study, the researchers studied the interaction between salicylic acid and HMGB1 by screening extracts prepared from human tissue culture cells to find proteins that could bind to salicylic acid. One of the proteins identified by them is HMGB1. The study has also identified a key suspect in neurodegenerative diseases like Alzheimer’s and Parkinson’s diseases, along with about two dozen additional candidates that have not been characterized yet.

Typically, HMGB1 is found inside the nucleus, but it can enter the blood stream when injured tissues or certain immune or cancer cells release it. The protein in the blood stream triggers inflammation by recruiting immune cells which prevents infections and repairs damaged tissues.

In order to find out more about the interactions between salicylic acid and HMGB1’s role in the body, Klessig worked with Marco Bianchi of San Raffaele University and Research Institute, who discovered that HMGB1 is a trigger of inflammation. They found that salicylic acid could block the recruitment and activation of immune cells at concentrations similar to those found in people on low-dose aspirin.

Bianchi said that they found that HMGB1 is involved in many disease conditions where the body confronts damage to its own cells. It's almost obvious that a very general anti-inflammatory compound blocks a very general inflammation trigger.

Klessig collaborated with biophysicist Gaetano Montelione at Rutgers to confirm that salicylic acid can bind to HMGB1, and also to identify the salicylic acid binding sites. They identified two derivatives of salicylic acid, which were found to be more effective than salicylic acid in blocking HMBG1’s pro-inflammatory activities. One of the compounds was synthesized in the lab, while the second one was isolated from a licorice plant – a Chinese medicinal herb.

Klessig said that they identified both synthetic and natural derivatives of salicylic acid which are about 50 to 1000 times more potent than salicylic acid or aspirin in suppressing the pro-inflammatory activity of extracellular HMGB1. This provides the proof of concept that more effective salicylic acid-based drugs are attainable.

References

https://medicalxpress.com/news/2015-09-key-insights-aspirin-disease-fighting-abilities.html

https://news.rutgers.edu/research-news/new-study-provides-key-insights-aspirin%E2%80%99s-disease-fighting-abilities/20150918#.VgZE1ZeELoc

How the Brain Encodes Time and Place

Nov 5, 2015

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Brain Activity

Our memory as we remember a particular experience has three main elements � what, when and where. In a new study which was published in a recent issue of Neuron, the scientists at the MIT have identified a brain circuit which they say processes the �when' and �where' elements of the memory. The work of this circuit, which links the hippocampus and a region of the brain called entorhinal cortex, is to separate location and timing into two streams of information. Two populations of neurons were identified in the entorhinal cortex by the researchers which convey this information, and they named them ��ocean cells' and �island cells.'

Hippocampus is a critical part of the brain known for its function of memory formation. Previous studies had suggested that it is the part of the brain that separates timing and context information. But, this new study says that this information is split well before it reaches the hippocampus.

Chen Sun, an MIT graduate student in brain and cognitive sciences and one of the lead authors of the paper said that their study suggest that there is a dichotomy of function upstream of the hippocampus. One pathway conveys temporal information into the hippocampus, and another which gives contextual representations to the hippocampus.

This study is a collaborative work of various authors which includes MIT postdoc Takashi Kitamura, senior author is Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and director of the RIKEN-MIT Center for Neural Circuit Genetics at MIT’s Picower Institute for Learning and Memory. Also there is Jared Martin, Stanford University graduate student Lacey Kitch, and Mark Schnitzer, an associate professor of biology and applied physics at Stanford.

The entorhinal cortex is located just outside the hippocampus, and it relays sensory information from other cortical areas to the hippocampus. A few years back Tonegawa and colleagues had identified island and ocean cells, and since then, they are working to discover their functions. Last year, Tonegawa's lab found that island cells, which form small clusters surrounded by ocean cells, are needed for the brain to form memories linking two events that occur in rapid succession. In the present study, the team has discovered that ocean cells are needed to note a location where an event took place.

Sun said that ocean cells are important for contextual representations. For every different setting – in the library, on the street, on the subway, etc., you have different memories associated with each different context. For the study, the researchers labeled the two cell populations with a fluorescent molecule that lights up when it binds to calcium�a signal that the neuron is firing. This let the team determine which cells were active during tasks requiring mice to link two events in time.

The team made use of a technique called optogenetics, which let them control neuron activity using light. They used it to investigate the changes in mice’s behavior when either island cells or ocean cells were silenced.

The firing rates of island cells depend on how fast the animal is moving which suggested that island cells help the animal navigate their way through space. On the other hand, ocean cells help the animal in recognizing where it is at a given time. It was also found that these two streams of information flow from the entorhinal cortex to different regions of the hippocampus – ocean cells send their contextual information to the CA3 and dentate gyrus regions, while island cells project to CA1 cells.

The team of researchers is now working to find how the entorhinal cortex and other parts of the brain represent time and place. They also aim to find how information on timing and location is processed in the brain to create the full memory of an event.

References

https://medicalxpress.com/news/2015-09-oceans-brain-contexts.html

https://bcs.mit.edu/news-events/news/how-brain-encodes-time-and-place

Differences between Tumors of Younger and Older Colorectal Cancer Patients

Nov 4, 2015

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Cases of colorectal cancers are on the rise in younger people. Doctors are of the opinion that some hereditary factors do play a role in its onset, but in majority of cases today it occurs spontaneously. Recent researches have led to the discovery that tumours in younger colorectal cancer patients could be molecularly distinct from those of older patients. These differences are related to the way genes are switched on and off (epigenetics) in the tumors of the younger patients. Such a discovery may lead to better treatment options tailored specifically to a younger age group, they say.

Colon Cancer

The results of the study will be presented to the 2015 European Cancer Congress by Dr. Andrea Cercek, an Assistant Attending Physician at the Memorial Sloan Kettering Cancer Center, and Assistant Professor of Medicine at Weill Cornell Medical Center, New York, USA. She is going to go over the details of her team’s analysis of genetic mutations in tumours from 126 patients under the age of 50 and 368 aged 50 and over. She says that it was interesting to find that there is a different frequency of mutation of genes known to be cancer-causing in the different age groups.

The tumours from the two groups of CRC patients were analysed � one group received treatment at Memorial Sloan Kettering and the other group were from The Cancer Genome Atlas – a project run by the US National Cancer Institute, with the goal to catalogue cancer-causing genetic mutations.

In order to look for gene mutations and other changes in the DNA which affects gene expression and methylation, genomic sequencing techniques were used. Those patients who had a very large number of mutations or had microsatellite instability issues were excluded. Dr. Cercek explained that in cancer both under (hypo) and over (hyper) methylation of genes are found. In the early onset group it was found that 154 genes were under-methylated. It was also seen that as age increased there was an increase in methylation in younger patients. This increase was far greater than what would occur naturally in normal tissue. This finding makes the researchers optimistic that tailored treatment can be designed to prevent or to improve the outcomes for the specific age group.

The Surveillance, Epidemiology, and End Result Registries (SEER), the agency that collects and collates cancer statistics on behalf of the US National Cancer Institute have revealed that there has been a continuous increase in CRC cases in younger people, at the rate of 1.5% per year in men and 1.6% per year in women during the period 1992-2011. Younger patients with CRC tend to be diagnosed later, when their disease is at a more advanced stage and therefore, more difficult to treat. The reason for this is a lack of awareness of symptoms in patients as well as doctors. Also, there is a tendency to attribute those symptoms to other causes.

Dr. Cercek opined that raising awareness of the increasing frequency of younger-onset CRC among doctors is very important. Even though there is no other difference in the therapies used it is seen that younger CRC patients are treated relatively more aggressively. The recent finding by the researchers is of significance so that they are able to develop better therapies for younger people, and improve their overall survival as well as their quality of life. Further research for identifying specific genetic patterns in CRC tumours in younger patients can lead to better treatment options.

Professor Peter Naredi, the ECCO scientific co-chair of the Congress, who was not a part of the research said that it is important to identify younger persons with a higher risk of CRC, and Dr. Cercek’s epigenetic analyses are an important step towards this.

References

https://medicalxpress.com/news/2015-09-differences-tumors-younger-older-colorectal.html

https://www.eurekalert.org/pub_releases/2015-09/eeco-dbt092415.php

Treating cancer by exploiting how its DNA is repaired

Nov 3, 2015

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The DNA is every cell of the body is constantly getting damaged and it is constantly getting repaired too by the cells' DNA repair system to keep it functioning well. There are times when the repair processes go wrong which marks the beginning of cancer. But, the surprising part is that these repair processes can be exploited to treat the disease.

For years, DNA repair mechanism has been the key focus for formulating cancer treatments. Courtesy that, today we have a new family of cancer drugs called PARP inhibitors. They exploit a weakness in cancer cells that already have faulty repair toolkits � like, cancers caused due to mistakes in the BCRA1 or 2 genes, which are crucial for DNA repair.

An important role was played by scientists from Cancer Research UK in the early development of PARP inhibitors. And the first of them, olaparib (Lynparza), is licensed for use within the EU for women with a certain type of ovarian cancer.

Our experts in the field, Professor Laurence Pearl, at the University of Sussex and his colleague (and wife) Dr. Frances Pearl, a computational biologist, are working further to discover new therapies and treatments.

Laurence explains that mistakes in our DNA can have disastrous consequences and hence, our cells have evolved a lot in their ways of repairing it. Still mistakes happen and it’s really important that cells protect their DNA and fix any damage as matter of priority. Our cells are equipped with a team of repair systems, known collectively as the DNA damage response – they work hard to keep things running smoothly. There are repair cells with different level of expertise to work on the most basic DNA repair job to rectify major faults. When repair work is on, essential functions in the cell will halt, like metabolism will slow down and cells will stop dividing. Small mistakes can be fixed quite easily, but too many mistakes are usually too bad to fix. In such an eventuality, the only solution is to admit defeat: the cell activates a self-destruct programme known as apoptosis.

Frances explains that all cancer cells have genetic mistakes or abnormalities which drive their growth. To carry on growing quickly they need to turn off some of their DNA checking and repair tools to tolerate these mistakes. The loss of this DNA ‘proofreading’ allows more mistakes to creep in, fueling more genetic chaos and driving tumour evolution. The surprising thing is, it is quite common for cancer cells to disable some of their molecular mechanics and it is quite frequent.

Understanding different molecular mechanics and the decision-making involved in repairing DNA can help in identifying new drug targets. By disabling the team members that check DNA is repaired properly, cancer cells are treading a fine line. If they get rid of too many of these cells and completely lose the ability to fix DNA, it can get very disorganized and the cell dies. This is something the researchers can take advantage and push cancer over the edge.

Traditional drug design is based on finding overactive molecules that are driving cancer, then blocking their activity but what Laurence and team are focusing on – is how to overcome the effects of molecules that are missing � so to say how to design drugs that inhibits the functions on which the cancer cells runs.

According to Laurence, there are two really promising avenues to try, to turn the idea into new therapies for patients. One is – cancer patients’ tumours can have faults in different parts of their DNA repair toolkits. If it can be figured out, exactly which DNA repair genes are faulty in a particular cancer, work can be done to figure out what type of damage it can’t fix. The second approach is developing drugs that take away parts of the cell which the cancer needs to survive.

Combining these two approaches might be even more successful. It has the potential to overcome cancers that have become resistant to chemotherapy. It’s clear that the DNA damage response is an area of weakness in cancer cells. It will be fascinating to see how further developments are made in this area.

References

https://medicalxpress.com/news/2015-09-cancer-exploiting-dna.html

https://www.cruk.cam.ac.uk/news/latest-news/expert-opinion-treating-cancer-exploiting-how-its-dna-repaired

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